• Morten S Thomsen and Jens D Mikkelsen.
• Neurobiology Research Unit, University Hospital Copenhagen, Rigshospitalet, Copenhagen, Denmark. morten.s.thomsen@nru.dk
• J. Neuroimmunol. 2012 Oct 15;251(1-2):65-72.

AbstractThe anti-inflammatory properties of, particularly the α7, nicotinic acetylcholine receptors (nAChRs) in the peripheral immune system are well documented. There are also reports of anti-inflammatory actions of nicotine in the CNS, but it is unclear, whether this is due to activation or inhibition of nAChRs. Here we investigate the mechanisms behind α7 nAChR-mediated modulation of TNF-α release. We show that α7 nAChR agonists or positive allosteric modulators do not affect LPS-induced release of the pro-inflammatory cytokine TNF-α from cultured microglia. This suggests that classical activation of, i.e. ion-flux through, the α7 nAChR does not reduce TNF-α release from activated microglia. Contrarily, the α7 nAChR antagonist methyllycaconitine and the weak (<10%) agonist NS6740 reduced LPS-induced TNF-α release, indicating that α7 nAChR antagonism conveys anti-inflammatory properties on microglia. The effect of methyllycaconitine or NS6740 was not due to changes in MAPK signaling. These results suggest that the anti-inflammatory effects of nicotine seen in vivo are not due to classical activation of the α7 nAChR, and further suggest that antagonism of α7 nAChRs may reduce neuroinflammation.Copyright © 2012 Elsevier B.V. All rights reserved.

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